Health-driven mechanism of organic food consumption: A structural equation modelling approach.

The COVID-19 pandemic seriously threatened human survival and development. It has also highlighted the significant correlation between ecological and public health. After three years of the COVID pandemic, Chinese consumers have become more aware of the importance of health. Especially in the Internet era, consumers' purchasing methods and health awareness have been changed. Consumers can buy nutritious and organic foods. To understand the impact of consumer psychology and health beliefs on the willingness to purchase organic food in the post-pandemic period, this study uses organic beef as an example and extracts key variables from three basic theories. The three basic theories include the Health Belief Model (HBM), the Theory of Planned Behavior (TPB), and the Norm Activation Model (NAM), respectively. Specifically, perceived susceptibility and severity are combined to form a health belief variable that can drive organic food purchasing. In contrast, perceived benefit, moral norms, self-efficiency, and controllability are introduced as mediating variables to construct the health driving factors of organic beef purchasing. Structural equation modeling (SEM) and mediation effect tests are used to analyse 539 samples. Meanwhile, paths and mechanisms between health concern and other variables are explored. The results show that health concern is an important driving factor. Health concern can significantly promote the formation of willingness to purchase organic beef. Mediation effect tests suggest that health concern can indirectly affect the willingness to purchase organic beef through perceived benefit, moral norms, and controllability, but the mediation effect of self-efficiency is not significant. This study provides important references for government regulation and certification of organic foods as well as for enterprises'organic food marketing strategies.

Exploring the Mechanisms of Sanguinarine in the Treatment of Osteoporosis by Integrating Network Pharmacology Analysis and Deep Learning Technology.

BACKGROUND: Sanguinarine (SAN) has been reported to have antioxidant, antiinflammatory, and antimicrobial activities with potential for the treatment of osteoporosis (OP). OBJECTIVE: This work purposed to unravel the molecular mechanisms of SAN in the treatment of OP. METHODS: OP-related genes and SAN-related targets were predicted from public databases. Differential expression analysis and VennDiagram were adopted to detect SAN-related targets against OP. Protein-protein interaction (PPI) network was served for core target identification. Molecular docking and DeepPurpose algorithm were further adopted to investigate the binding ability between core targets and SAN. Gene pathway scoring of these targets was calculated utilizing gene set variation analysis (GSVA). Finally, we explored the effect of SAN on the expressions of core targets in preosteoblastic MC3T3-E1 cells. RESULTS: A total of 21 candidate targets of SAN against OP were acquired. Furthermore, six core targets were identified, among which CASP3, CTNNB1, and ERBB2 were remarkably differentially expressed in OP and healthy individuals. The binding energies of SAN with CASP3, CTNNB1, and ERBB2 were -6, -6.731, and -7.162 kcal/mol, respectively. Moreover, the GSVA scores of the Wnt/calcium signaling pathway were significantly lower in OP cases than in healthy individuals. In addition, the expression of CASP3 was positively associated with Wnt/calcium signaling pathway. CASP3 and ERBB2 were significantly lower expressed in SAN group than in DMSO group, whereas the expression of CTNNB1 was in contrast. CONCLUSION: CASP3, CTNNB1, and ERBB2 emerge as potential targets of SAN in OP prevention and treatment.

Widely targeted quantitative lipidomics reveal lipid remodeling in adipose tissue after long term of the combined exposure to bisphenol A and fructose.

Adipose tissue is the main organ that stores lipids and it plays important roles in metabolic balance in the body. We recently reported in Human and Experimental Toxicology that the combined exposure to BPA and fructose may interfere with energy metabolism of adipose tissue. However, it is still unclear whether the combined exposure to BPA and fructose has the possibility to induce lipid remodeling in adipose tissue. In the present study, we performed a widely targeted quantitative lipidomic analysis of the adipose tissue of rats after 6 months of BPA and fructose combined exposure. We totally determined 734 lipid molecules in the adipose tissue of rats. Principal component analysis (PCA) showed the group of the combined exposure to higher-dose (25 µg/kg every other day) BPA and fructose can be distinguished from the groups of control, higher-dose BPA exposure and fructose exposure clearly. Partial least squares-discriminant analysis (PLS-DA) and univariate statistical analysis displayed lipids of PC(18:0_ 20:3), TG(8:0_14:0_16:0), TG(12:0_14:0_16:1), TG(10:0_16:0_16:1), TG(12:0_ 14:0_18:1), TG(14:0_ 16:0_16:1), TG(14:0_14:1_16:1), TG(8:0_ 16:1_16:2), TG(14:1_16:1_ 16:1), TG(16:1_18:1_18:1), TG(16:0_16:1_20:4) and TG(15:0_18:1_ 24:1) may contributed the most to the discrimination. These findings indicated that combined exposure to BPA and fructose has the potential to cause lipid remodeling in adipose tissue.

Resilience of agricultural development in China's major grain-producing areas under the double security goals of "grain ecology".

The development of agriculture faces uncertainties due to global climate variability and the scarcity of agricultural resources. Enhancing agricultural development resilience is essential for improving agriculture's adaptability to the external environment and ensuring food security. It is imperative to prevent and control agricultural pollution as it worsens. Thus, enhancing the resilience of agricultural development requires balancing food security and ecological security. The present study constructs an evaluation system for agricultural development resilience in China with three levels: resistance, resilience, and reengineering ability. The agricultural development resilience of China's main grain-producing areas is evaluated using the entropy method, and regional differences are analyzed using kernel density estimation and the Theil index. The obstacle model was used to identify and analyze the obstacles that affect agricultural development's resilience to propose countermeasures. The results showed that (1) agricultural development resilience in China's main grain-producing areas has steadily increased from 0.317 to 0.427. The resilience of agrarian development in Heilongjiang, Shandong, and Henan provinces ranges from 0.473 to 0.575, which is far higher than the mean development level; (2) Regional differences in the main grain-producing areas are narrowing from 0.077 to 0.023; (3) The main grain-producing areas share common obstacle factors, emphasizing the critical role of technological innovation, investment, and machine-cultivated land resources in enhancing agricultural resilience against external risks. Paying attention to the amount of fertilizer usage is crucial to achieving ecological security goals.

Anesthesia-related intervention for long-term survival and cancer recurrence following breast cancer surgery: A systematic review of prospective studies.

OBJECTIVE: Anesthesia is correlated with the prognosis of cancer surgery. However, evidence from prospective studies focusing on breast cancer is currently limited. This systematic review aimed to investigate the effect of anesthesia-related interventions on oncological outcomes following breast cancer surgery in prospective studies. METHODS: Literature searches were performed from inception to June. 2023 in the Pubmed, Web of Science, Embase, and ClinicalTrials databases. The main inclusion criteria comprised a minimum of one-year follow-up duration, with oncological outcomes as endpoints. Anesthesia-related interventions encompassed, but were not limited to, type of anesthesia, anesthetics, and analgesics. The risk of bias was assessed using the Cochrane Risk of Bias Tool. RESULTS: A total of 9 studies were included. Anesthesia-related interventions included paravertebral nerve block (3), pectoral nerve block (1), sevoflurane (2), ketorolac (2), and infiltration of lidocaine (1). Cancer recurrence, metastasis, disease-free survival, or (and) overall survival were assessed. Among all included studies, only infiltration of lidocaine was found to prolong disease-free survival and overall survival. CONCLUSION: Regional anesthesia and propofol did not improve oncological outcomes following breast cancer surgery. The anti-tumorigenic effect of ketorolac warrants future studies with larger sample sizes. Perioperative infiltration of lidocaine around the tumor may be a promising anti-tumorigenic intervention that can prolong overall survival in patients with early breast cancer.

The effect of fructose exposure on amino acid metabolism among Chinese community residents and its possible multi-omics mechanisms.

The consumption of fructose has increased dramaticly during the last few decades, inducing a great increase in the risk of intrahepatic lipid accumulation, hypertriglyceridemia, hyperuricemia and cancer. However, the underlying mechanism has not yet been fully elucidated. Amino acid metabolism may play an important role in the process of the diseases caused by fructose, but there is still a lack of corresponding evidence. In present study, we provide an evidence of how fructose affects amino acids metabolism in 1895 ordinary residents in Chinese community using UPLC-QqQMS based amino acid targeted metabolomics and the underlying mechanism of fructose exposure how interferes with amino acid metabolism related genes and acetylated modification of proteome in the liver of rats model. We found people with high fructose exposure had higher levels of Asa, EtN, Asp, and Glu, and lower levels of 1MHis, PEtN, Arg, Gln, GABA, Aad, Hyl and Cys. The further mechanism study displayed amino acid metabolic genes of Aspa, Cndp1, Dbt, Dmgdh, and toxic metabolites such as N-acetylethanolamines accumulation, interference of urea cycle, as well as acetylated modification of key enzymes in glutamine metabolic network and glutamine derived NEAAs synthesis pathway in liver may play important roles in fructose caused reprogramming in amino acid metabolism. This research provides novel insights of the mechanism of amino acid metabolic disorder caused by fructose and supplies new targets for clinical therapy.

Impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue.

Background: Adipose tissue is a dynamic endocrine organ that plays a key role in regulating metabolic homeostasis. Previous studies confirmed that bisphenol A (BPA) or fructose can interfere with the function of adipose tissue. Nonetheless, knowledge on how exposure to BPA and fructose impacts energy metabolism in adipose tissue remains limited.Purpose: To determine impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue.Method: 57 energy metabolic intermediates in adipose tissue and 7 adipocytokines in serum from Sprague Dawley rats were examined after combined exposure to two levels of BPA (lower dose: 0.25, and higher dose: 25 µg/kg every other day) and 5% fructose for 6 months.Results: combined exposure to lower-dose BPA and fructose significantly increased omentin-1, pyruvic acid, adenosine triphosphate (ATP), adenosine monophosphate (AMP), inosine monophosphate (IMP), inosine, and l-lactate; however, these parameters were not significantly affected by higher-dose BPA combined with fructose. Interestingly, the level of succinate (an intermediate of the citric acid cycle) increased dose-dependently in adipose tissue, and the level of apelin 13 (a versatile adipocytokine) decreased dose-dependently in serum after combined exposure to BPA and fructose. Phosphoenolpyruvic acid, phenyl-lactate, and ornithine were significantly correlated with asprosin, omentin-1, apelin, apelin 13, and adiponectin, while l-tyrosine was significantly correlated with irisin and a-FABP under combined exposure to BPA and fructose.Conclusions: these findings indicated that lower-dose BPA combined with fructose could amplify the impact on glycolysis, energy storage, and purine nucleotide biosynthesis in adipose tissue, and adipocytokines, such as omentin-1 and apelin 13, may be related to metabolic interference induced by BPA and fructose exposure.

Hypoglossal nerve delineation in nasopharyngeal carcinoma patients may reduce the radiation dose and damage to the nerve.

This study aims to establish a delineation guideline for the contouring of the hypoglossal nerve by dividing the nerve into different segments, and to test the possibility of a radiation dose reduction to the hypoglossal nerve in NPC patients receiving radiotherapy. Twenty NPC patients were selected arbitrarily. The hypoglossal nerves were delineated using anatomic landmarks and divided into the cisternal, intracanalicular, carotid, and transverse segments. The tumor coverage by radiation and dose-volume parameters of the nerve with and without various dose constraints to the hypoglossal nerve were compared. The hypoglossal nerve, which is invisible on CT images, can be delineated accurately with the assistance of several anatomic landmarks. Without a dose constraint to the hypoglossal nerve, the carotid space, intracanalicular, and transverse segments had high radiation dose-volumes. The dose-volume to the nerve, however, can be reduced when the nerve was defined and a dose constraint was given. The delineation of the hypoglossal nerve with its different segments is feasible. The carotid space, intracanalicular, and transverse segments received the highest dose, where the nerve damage was most likely located. The dose to the nerve can be reduced to less than 70 Gy using the intensity-modulated radiotherapy technique.

Incidence of postoperative hypothermia and shivering and risk factors in patients undergoing malignant tumor surgery: a retrospective study.

BACKGROUND: Perioperative hypothermia and shivering are common and can cause adverse outcomes. The aim of this study was to investigate the incidence of postoperative hypothermia and shivering and their risk factors in patients undergoing malignant tumor surgery. METHODS: This retrospective study collected data from patients with American Society of Anesthesiologists physical status (ASA) I or II who underwent scheduled surgery from November 2020 to March 2021 at Fudan University Shanghai Cancer Center. Each patient's core body temperature was measured at three time points: time point 1 (arrival at the postanesthesia care unit (PACU)), time point 2 (after 30-min care in the PACU), and time point 3 (at discharge from the PACU). At time point 1, if the patient's body temperature was below 36 ℃, we provided an active forced-air warmer. At time point 2, if it was still below 36 ℃, the forced-air warmer was still applied until the patient was discharged from the PACU. If it reached 36 ℃, the forced-air warmer would be switched off. Univariate and multivariate logistic regression combined with stepwise methods and linear regression were used to explore risk factors for postoperative hypothermia and shivering. RESULTS: The numbers (percentage) of 202 patients who developed postoperative hypothermia at the different time points were 52 (25.7%), 37 (18.3%) and 28 (13.9%). Eight patients (4.0%) experienced shivering. Multivariate logistic regression showed that high weight (OR = 0.923, 95% CI: 0.884 to 0.964, P = 0.0003) and low estimated blood loss (OR = 0.252, 95% CI: 0.115 to 0.550, P = 0.0005) were protective factors against hypothermia, while long surgical duration (OR = 3.339, 95% CI: 1.675 to 6.655, P = 0.0006) was an independent risk factor for hypothermia at time point 1. There was no risk factor associated with the occurrence of shivering (P > 0.05). There was a significant difference between the hypothermia and normothermia groups in the median length of stay in the PACU (59.0 vs. 49.0 min, P = 0.0123). CONCLUSIONS: Postoperative hypothermia occurred frequently. Weight, estimated blood loss and surgical duration were significantly associated with hypothermia on arrival at the PACU.

Exposure to SARS-CoV-2 generates T-cell memory in the absence of a detectable viral infection.

T-cell immunity is important for recovery from COVID-19 and provides heightened immunity for re-infection. However, little is known about the SARS-CoV-2-specific T-cell immunity in virus-exposed individuals. Here we report virus-specific CD4+ and CD8+ T-cell memory in recovered COVID-19 patients and close contacts. We also demonstrate the size and quality of the memory T-cell pool of COVID-19 patients are larger and better than those of close contacts. However, the proliferation capacity, size and quality of T-cell responses in close contacts are readily distinguishable from healthy donors, suggesting close contacts are able to gain T-cell immunity against SARS-CoV-2 despite lacking a detectable infection. Additionally, asymptomatic and symptomatic COVID-19 patients contain similar levels of SARS-CoV-2-specific T-cell memory. Overall, this study demonstrates the versatility and potential of memory T cells from COVID-19 patients and close contacts, which may be important for host protection.

5HTTLPR polymorphism and postpartum depression risk: A meta-analysis.

OBJECTIVE: Postpartum depression (PPD) is an episode of major depressive disorder that affecting women of childbearing age. 5-HTTLPR is 1 of the most extensively investigated polymorphisms in PPD. However, the previous results were inconsistent and inclusive. Hence, we performed a meta-analysis to precisely evaluate the association between 5-HTTLPR polymorphism and PPD susceptibility. METHODS: The studies were retrieved through databases including PubMed, web of science, EMASE, and CNKI. The odd ratios (ORs) and 95% confidence interval (CIs) were applied for evaluating the genetic association between 5-HTTLPR (L/S) polymorphism and PPD risk. RESULTS: Six studies with 519 cases and 737 controls were enrolled in the present study. The frequencies of allelic (OR = 0.72, 95%CI = 0.60-0.85, P = .0001) and dominant (OR = 0.57, 95%CI = 0.44-0.73, P = .004) models of 5-HTTLPR polymorphism significantly decreased in patients with PPD than those in the healthy controls. Subgroup analysis based on ethnicity revealed that the allelic (OR = 0.71, 95%CI = 0.60-0.85, P = .0001) and dominant (OR = 0.51, 95%CI = 0.32-0.79, P = .003) models of 5-HTTLPR polymorphism were significantly associated with PPD risk in Asian population (P > .05). No evidence was observed between the recessive model of 5-HTTLPR polymorphism and PPD risk (P > .05). CONCLUSIONS: The allelic and dominant models of 5-HTTLPR polymorphism might be protective factors for PPD. To confirm these results, larger number of association studies or multicenter case-control studies are necessary in the future.

The GCAG Haplotype of the CRHBP Gene May Decrease the Risk for Robbery Behavior Among the Han Chinese.

Aims: Hypothalamic-pituitary-adrenocortical axis gene polymorphisms have been reported to affect aggressive behavior. Corticotropin releasing hormone binding protein (CRHBP) polymorphisms have been shown to contribute to the susceptibility to stress-related disorders, including aggressive behavior. However, no study has been conducted on the relationship between CRHBP polymorphisms and aggressive behavior risk in the Han Chinese population. Methods: A case-control study that comprised 194 male criminals and 303 healthy controls was carried out to investigate the genetic association between several CRHBP gene polymorphisms and aggressive behavior risk in the Hunan Han population. Genotyping was conducted by using the improved multiplex ligase detection reaction method for four CRHBP loci: rs10062367, rs32897, rs7718461, and rs7721799. Results: The incidence of the rs32897C allele was significantly lower in the robbery group compared with the control subjects after a Bonferroni correction (p = 0.016), indicating a protective role for the C allele of rs32897. Interestingly, a haplotypic analysis that was stratified by robbery and intentional injury showed that the haplotype consisting of rs10062367G, rs32897C, rs7718461A, and rs7721799G (which includes the protective rs32897 C allele) was significantly associated with decreased robbery risk (odds ratio [OR] = 0.31, p = 0.0005), but not for intentional injury (OR = 0.82, p = 0.44). The haplotype consisting of rs10062367G, rs32897T, rs7718461A, and rs7721799G carrying the rs32897 T allele significantly increased the risk for robbery (OR = 1.47, p = 0.0213), but not for intentional injury (OR = 0.92, p = 0.64). Conclusions: The rs32897 alleles and the haplotypes containing the rs32897 alleles, including GCAG and GTAG, may be factors associated with committing robbery in the Hunan Han population, and could be used to provide clinical counseling with regard to aggressive behavior. However, further studies including multiple ethnicities are needed.

A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir.

Remdesivir (GS-5734), a viral RNA-dependent RNA polymerase (RdRP) inhibitor that can be used to treat a variety of RNA virus infections, is expected to be an effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. On May 1, 2020, The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for remdesivir to treat COVID-19 patients. In light of the COVID-19 pandemic, this review presents comprehensive information on remdesivir, including information regarding the milestones, intellectual properties, anti-coronavirus mechanisms, preclinical research and clinical trials, and in particular, the chemical synthesis, pharmacology, toxicology, pharmacodynamics and pharmacokinetics of remdesivir. Furthermore, perspectives regarding the use of remdesivir for the treatment of COVID-19 are also discussed.

The association between IL18, FOXP3 and IL13 genes polymorphisms and risk of allergic rhinitis: a meta-analysis.

OBJECTIVES: Allergic rhinitis (AR) is a chronic inflammatory disease of nasal mucosa. Loss of function of Th17 cells and regulatory T (Treg) cells plays a role in the pathogenesis of AR. IL18, FOXP3, and IL13 are key genes in the development of AR. However, the genetic associations between IL18, FOXP3 and IL13 genes polymorphisms and AR risk were inconclusive yet. METHODS: A meta-analysis was performed by searching through Pubmed, EMBASE, web of science and CNKI databases. The ORs and 95%CIs were used to assess the genetic association between the allelic, dominant and recessive models of IL18, FOXP3 and IL13 genes polymorphisms and AR risk. RESULTS: A total of 15 articles (6 for FOXP3, 5 for IL18, and 5 for IL13) were enrolled in the present study. No association was detected between the IL18 rs187238, rs1946518, rs360721, FOXP3 rs2232365, rs3761548 and IL13 rs1800925 polymorphisms and AR risk (p > 0.05). Significant associations were observed between the allelic (p = 0.001, OR 1.32, 95% CI 1.12-1.56), dominant (p = 0.005, OR 1.43, 95% CI 1.11-1.83) and recessive models (p = 0.01, OR 1.64, 95% CI 1.13, 2.40) of IL13 rs20541 and AR risk. Subgroup analysis based on ethnicity revealed that the IL13 rs20541 was significantly associated with AR risk in Asian population (allelic model: p = 0.009, OR 1.36, 95% CI 1.13-1.63, dominant model: p = 0.005, OR 1.43, 95% CI 1.11-1.83; recessive model: p = 0.01, OR 1.64, 95% CI 1.13-2.40). CONCLUSIONS: IL13 rs20541 may contribute to the risk of AR in Asian population. To confirm these results, larger number of case-control study with more subjects is necessary in the future.

Significance-based multi-scale method for network community detection and its application in disease-gene prediction.

Community detection in complex networks is an important issue in network science. Several statistical measures have been proposed and widely applied to detecting the communities in various complex networks. However, due to the lack of flexibility resolution, some of them have to encounter the resolution limit and thus are not compatible with multi-scale structures of complex networks. In this paper, we investigated a statistical measure of interest for community detection, Significance [Sci. Rep. 3 (2013) 2930], and analyzed its critical behaviors based on the theoretical derivation of critical number of communities and the phase diagram in community-partition transition. It was revealed that Significance exhibits far higher resolution than the traditional Modularity when the intra- and inter-link densities of communities are obviously different. Following the critical analysis, we developed a multi-resolution version of Significance for identifying communities in the multi-scale networks. Experimental tests in several typical networks have been performed and confirmed that the generalized Significance can be competent for the multi-scale communities detection. Moreover, it can effectively relax the first- and second-type resolution limits. Finally, we displayed an important potential application of the multi-scale Significance in computational biology: disease-gene identification, showing that extracting information from the perspective of multi-scale module mining is helpful for disease gene prediction.

Antitumor effects and mechanisms of 1,25(OH)2D3 in the Pfeiffer diffuse large B lymphoma cell line.

Diffuse large B cell lymphoma (DLBCL) represents the most common subtype of non­Hodgkin lymphoma in China. 1,25­Dihydroxyvitamin D3 [1,25(OH)2D3] has been shown to possess significant antitumor potential and is degraded by 25­hydroxyvitamin D­24­hydroxylase (CYP24A1). In the present study, the role of CYP24A1 and autophagy, and their underlying mechanisms in the anticancer effects of 1,25(OH)2D3 in DLBCL cells, were investigated. It was found that the levels of CYP24A1 in DLBCL lymph node tissues were higher than in hyperplasia lymphadenitis tissue. Moreover, the expression of CYP24A1 was positively associated with the Ann Arbor stage and the International Prognostic Index in patients with DLBCL, and negatively associated with the clinical response to treatment. Patients >60 years of age were found to have a higher level of CYP24A1. 1,25(OH)2D3 inhibited the proliferation of the Pfeiffer DLBCL cell line and increased the G1 phase population of Pfeiffer cells. Rapamycin (RAPA) in combination with 1,25(OH)2D3 increased the G1 phase distribution of Pfeiffer cells. Furthermore, RAPA blocked the increase of CYP24A1 and vitamin D receptor (VDR) expression induced by 1,25(OH)2D3. 1,25(OH)2D3 induced the formation of autophagosomes, increased the expression of autophagy related protein light chain (LC)3II/LC3I and reduced the expression of the ubiquitin binding protein P62. In addition, 1,25(OH)2D3 decreased the phosphorylation of AKT and mammalian target of RAPA (mTOR), and downstream targets eukaryotic translation imitation factor 4E­binding protein 1 and ribosomal protein S6 kinase ß­1 in Pfeiffer cells. The results from the present study suggested that CYP24A1 may be a novel prognostic indicator for DLBCL. 1,25(OH)2D3 inhibited proliferation and induced autophagy of Pfeiffer cells. In addition, 1,25(OH)2D3 increased the G1 phase population of Pfeiffer cells. These effects may be mediated by inhibition of the AKT/mTOR/PI3K signaling pathway. RAPA increased the cell cycle arrest induced by 1,25(OH)2D3 by blocking the upregulated expression of CYP24A1 and VDR.

Long noncoding RNA-regulator of reprogramming alleviates hypoxia-induced cerebral injury in mice model and human via modulating apoptosis complexes.

Ischemic stroke causes cerebral hypoxia, while long non-coding RNA regulator of reprogramming is associated with hypoxia. To find a new intervention target to protect hypoxic cerebral tissue and a potential biomarker from reflecting the severity of hypoxia after ischemic stroke, our research explored the expression pattern and function of the regulator of reprogramming in cerebral hypoxia-induced injury. The expression pattern and the function of the regulator of reprogramming were explored in mice with middle cerebral artery occlusion, and human brain microvascular endothelial cells underwent oxygen-glucose deprivation treatment. A case-control study, including 223 ischemic stroke patients and 155 controls were also conducted to investigate its correlation with ischemic stroke clinical characteristics. Results showed that the regulator of reprogramming increased significantly in middle cerebral artery occlusion in mice (P < 0.05), and its level remained stable within 2 to 48 h after the implement of middle cerebral artery occlusion. Oxygen-glucose deprivation up-regulated the expression of regulator of reprogramming, and regulator of reprogramming promoted ASK-1/STRAP/14-3-3 complex formation to inhibit the activation of TNF-α/ASK-1-mediated apoptosis of human brain microvascular endothelial cells, while small interfering ribonucleic acid (RNA) targeting regulator of reprogramming amplified these effects. Regulator of reprogramming increased and maintained stable within 3 to 48 h of ischemic stroke onset in patients, and was negatively associated with the National Institutes of Health Stroke Scale (NIHSS) (r = -0.708, P < 0.001), high sensitivity C-reactive protein (Hs-CRP) (r = -0.683, P < 0.001) level, infarct volume (r = -0.579, P < 0.001), and modified Rankin scale (mRS) (r = -0.728, P < 0.001). These results indicate that the regulator of reprogramming can alleviate cerebral hypoxia-induced injury by suppressing TNFα-induced apoptosis of vascular endothelial cells.

Influence of natural variation in berry size on the volatile profiles of Vitis vinifera L. cv. Merlot and Cabernet Gernischt grapes.

This study was conducted during the 2014 and 2015 vintages on Vitis vinifera L. cv. Merlot and Cabernet Gernischt to investigate whether natural variation in berry size could affect grape aromatic compounds. Grape berries were separated into three size categories based on their diameter: small, middle and large. The results showed that berry size exerted a significant influence on the volatile profiles of both winegrape varieties. Hierarchical clustering analysis demonstrated that the volatile profiles of middle berries were different from those of large and small berries. Middle berries had the greatest abundance of aroma compounds, followed by small and large berries. Especially, C6/C9 compounds, norisoprenoids, terpenoids showed markedly different concentrations among differently sized Merlot berries and C6/C9 compounds, terpenoids among differently sized Cabernet Gernischt berries. Middle berries of both grape varieties may possess the greatest intensity of fresh-green, fruity and floral aromas due to the high odour activity values (OAVs) of decanal, hexanal, (E)-2-hexenal, (E)-ß-damascenone and ß-ionone in middle sizes of Merlot berries and the high OAVs of (E)-2-hexenal and (E)-ß-damascenone in middle sizes of Cabernet Gernischt berries. This knowledge could be important for winemakers to conduct targeted berry sorting, thereby improving the aromatic quality of grapes.

MicroRNA expression profiling in human acute organophosphorus poisoning and functional analysis of dysregulated miRNAs.

OBJECTIVE: Acute organophosphorus(OP) pesticide poisoning is associated with dysfunctions in multiple organs, especially skeletal muscles, the nervous system and the heart. However, little is known about the specific microRNA (miRNA) changes that control the pathophysiological processes of acute OP poisoning damage. We aimed to explore miRNA expression profiles and gain insight into molecular mechanisms of OP toxic effects. METHODS: MicroRNA expression was analyzed by TaqMan Human MicroRNA Array analysis and subsequent validated with quantitive PCR. The targets of the significantly different miRNAs were predicted with miRNA prediction databases, and pathway analysis of the predicted target genes was performed using bioinformatics resources. RESULTS: 37 miRNAs were significantly different in the sera of poisoned patients compared to the healthy controls, including 29 miRNAs that were up-regulated and 8 miRNAs that were down-regulated. Functional analysis indicated that many pathways potentially regulated by these miRNAs are involved in skeletal muscle, nervous system and heart disorders. CONCLUSION: This study mapped changes in the serum miRNA expression profiles of poisoning patients and predicted functional links between miRNAs and their target genes in the regulation of acute OP poisoning. Our findings are an important resource for further understanding the role of these miRNAs in the regulation of OP-induced injury.

Synthesis and in vitro and in vivo antitumour activity study of 11-hydroxyl esterified bergenin/cinnamic acid hybrids.

Fourteen bergenin/cinnamic acid hybrids were synthesized, characterized and evaluated for their antitumour activity both in vitro and in vivo. The most potent compound, 5c, arrested HepG2 cells (IC50 = 4.23 ± 0.79 µM) in the G2/M phase and induced cellular apoptosis. Moreover, compound 5c was also found to suppress the tumour growth in Heps xenograft-bearing mice with low toxicity. In the mechanistic study, 5c administration ignited a mitochondria-mediated apoptosis pathway of HepG2 cell death. Furthermore, 5c activated Akt-dependent pathways and further decreased the expression of the Bcl-2 family of proteins. The downstream mitochondrial p53 translocation was also significantly activated, accompanied by an increase of the caspase-9, caspase-3 activation. These data imply that bergenin/cinnamic acid hybrids could serve as novel Akt/Bcl-2 inhibitors for further preclinical studies.